PROJECT SUMMARY/ABSTRACT Endocrine therapy (ET) is an inexpensive, non-toxic and highly effective cornerstone therapy for hormone receptor-positive (HR+) breast cancer that relies on long-term adherence to oral medication. Of 230,000 estimated new breast cancer cases in the United States each year, more than 80% have an HR+ phenotype and are candidates for ET, which decreases breast cancer mortality by 40% or more. Despite this substantial benefit, approximately half of patients discontinue or become non-adherent to ET before completing the recommended minimum treatment duration of five years. ET under-use, including early discontinuation and non-adherence (missing more than 20% of prescribed doses), is solidly linked to increased breast cancer recurrence and decrements in survival. ET under-use is more prevalent in black and young (<50 yrs) women and may contribute to outcome disparities in these groups. Although medication adherence is a clearly documented crisis in breast cancer care, no evidence-based strategy exists for optimizing ET adherence. Effective interventions to support ET use in diverse patient populations are urgently needed. The long-term goal of this research is to improve survival and reduce disparities in HR+ breast cancer by optimizing the delivery of widely available, highly effective and cost-effective ET through interventions to support ET adherence. Our preliminary work has demonstrated the feasibility, acceptability, and early promise of effectiveness of both lower-intensity mobile text message reminders (TMR) and higher-intensity telephone-based motivational interviewing (MI) counseling for ET adherence. The objective of this application is to conduct a multisite randomized clinical trial of TMR, MI, or the combination of both, versus usual care, through the Alliance for Clinical Trials in Oncology network. We will compare ET adherence at 12 and 24 months in diverse women exposed to TMR, telephone-based MI, or both, versus usual care (Aim 1). We will then evaluate the effects of TMR, MI, and TMR+MI interventions on patient- reported outcomes including medication use self-efficacy, health related quality of life, cancer worry, and knowledge and attitudes about ET, relative to usual care (Aim 2). Finally, we will estimate the incremental cost and cost-effectiveness of delivering TMR, MI, and TMR+MI interventions, relative to usual care (Aim 3). The rationale for this research is that effective and low-cost oral anticancer adherence interventions can have a substantial impact on HR+ breast cancer survival and disparities among black and younger women by increasing the long-term adherence to efficacious treatments.